PHAGE PRODUCTION AND PHAGE PRECURSOR 337 



by lytic enzymes other than those derived from bacteria or phage, Lysozyme, for instance, 

 will enhance the action of cholera phage (White 1937). 



Pirie (1939) observed an increase in reducing sugars and a decrease in precipitable 

 carbohydrate during lysis by coh phage. No enzyme was detected in the phage itself, 

 but the coU baciUus yielded an enzyme that attacked the bacterial cellular polysac- 

 charides. Though no direct comiection exists between this phenomenon and lysis by the 

 phage, the association of lysis with the enzymic destruction of those ceUular elements 

 known to adsorb phage is at least suggestive. In a later paper (1940) Pirie records the 

 release of adsorbed phage from B. megatherium by treatment with lysozyme, and the 

 destruction of the bacterium's capacity to absorb phage by prehminary incubation with 

 lysozyme. The lysozyme hydrolysed a carbohydrate present in B. megatherium, and, 

 as Pirie suggests, it is possible that carbohydrate is one that determines the specific absorp- 

 tion of the phage. 



Phage Production and Phage Precursor. 



The rapid production of phage from bacteria following the adsorption of one 

 or a few phage particles has suggested to some workers the possibility that the 

 substances of bacterial origin from which the jihage is derived exist as a precursor 

 requiring only a few comparatively small transformations to convert it into phage. 

 The analogy of the activation of a pepsinogen by a pepsin has been cited in this 

 connection. It breaks down, however, in one important respect, for with the 

 activation of enzyme precursors by similar enzymes, it is the nature of the precursor 

 which determines the enzyme produced. Thus chicken pepsin converts swine 

 pepsinogen into swine pepsin, and swine pepsin converts chicken pepsinogen into 

 chicken pepsin (Herriott, Bartz and Northrop 1938). A bacterium, on the 

 other hand, may be attacked by several distinct phages, and each phage reproduces 

 itself. If a single phage precursor is postulated, it must then be sufficiently primi- 

 tive in form to yield a variety of phages when suitably activated. Krueger and 

 Baldwin (1937) made a cell-free extract of staphylococci in the presence of which 

 the titre of a phage j&ltrate doubled in 2 hours. In staphylococci, this phage 

 precursor was more easily destroyed than either the cells which produced it, or 

 the phage into which it was converted. Apparently protein in nature, its activity 

 was reduced by antistaphylococcal serum, by heating to 45° C. for 20 minutes, by 

 iodoacetic acid, and by light in the presence of methylene blue. It was not liberated 

 from cells disintegrated by sonic vibrations (see Krueger, Scribner and Mecracken 

 1940, Krueger, Brown and Scribner 1941). 



Spizizen (19436) has opened up a new field in the study of phage precursors 

 by applying the methods elaborated by workers on bacterial nutrition to the 

 study of phage production by Bad. coli in phosphate buffer. Several amino-acids, 

 certain phosphorylated compounds (including nucleic acid and co-enzyme I), 

 4-carbon dicarboxylic acids, and ferric, ferrous, magnesium and manganese ions, 

 stimulated phage production. Glycine and glycine anhydride were particularly 

 effective in this respect, inducing a marked increase in phage in the absence of 

 bacterial multiplication. The production of phage was even greater if the organisms 

 were exposed to the glycine anhydride for several hours before the addition of 

 the infecting dose of phage, suggesting that, in the interval, the cells either had 

 adapted themselves to a more rapid glycine metabolism, or had built up reserves 

 of a phage precursor. It appears that certain fundamental metabolic processes 

 in the cell are required for phage multiplication but not necessarily all the processes 

 that lead to cell multiplication. The specificity of some of these processes is illus- 

 trated by the fact that the action of glycine was specifically inhibited by the 



